In this study, pulmonary tuberculosis was treated on an ambulatory basis, with the patients engaging in their usual activities and with a shortened period of chemotherapy. During the first year of the study, patients with pulmonary tuberculosis were randomly included in one of the following two groups: (1) group 1 received isoniazid (5 to 6 mg/kg of body weight), ethambutol (25 mg/kg), and rifampin (rifampicin, 10 mg/kg) daily for a total of six months; and (2) group 2 received the same therapy as group 1, but treatment was continued for a further six months with only isoniazid (5 mg/kg three days per week). At the beginning of the second year of the study, all subsequent patients included in the study were placed into group 1. Of the 163 patients who started the study, 136 patients (99 from group 1 and 37 from group 2) completed the treatment and converted their bacteriologic findings. There was one relapse in group 1. Adverse reactions were observed in six patients, but they did not have to interrupt treatment.

Patients with acute myocardial infarction are frequently not fed hot and cold liquids because of possible deleterious effects on heart rate, blood pressure, and cardiac rhythm. In an attempt to identify and quantify such changes, hot liquid with a temperature in excess of 70 degrees C and cold liquid at an average temperature of 7 degree C were ingested by 20 patients within 36 hours of documented myocardial infarction and by 11 control patients with severe anginal episodes or chest wall syndromes. Heart rate and rhythm were continuously monitored during ingestion of the hot and cold liquids, and blood pressure was recorded intermittently. No patient in either group had a change in cardiac rhythm or an increase in ectopy during ingestion of the hot and cold liquids. Changes in blood pressure and heart rate were also not significant during liquid ingestion by patients with infarction and control patients. The practice of avoiding ingestion of hot and cold liquids by patients with acute myocardial infarction is not supported by these observations.

Ipratropium bromide (also known as Sch 1000) is a new atropine-like bronchodilator drug whose mechanism of action is via an anticholinergic pathway and may decrease cyclic guanosine monophosphate. Although of established efficacy in asthma, there are no studies of the use of ipratropium in patients with chronic bronchitis. The single metered aerosol doses of 10 mug, 20 mug, 40 mug and 80 mug of ipratropium bromide, 75 mug and 150 mug of isoproterenol, and placebo were studied in 20 adult patients, half with asthma and half with chronic bronchitis. To qualify, all patients demonstrated at least 20% improvement in the forced expiratory volume in one second while in the drug-free state when tested with isoproterenol. All subjects were tested for six hours with each agent in a double-blind crossover design. The dose-response aspects of the study indicate that in bronchial asthma the optimal range of dosage is 40 mug to 80 mug of ipratropium bromide. These doses are superior to isoproterenol in duration of action. In chronic bronchitis, all doses of ipratropium showed prolonged efficacy, but 80 mug was superior. Isoproterenol lacked this sustained efficacy. No significant alteration in pulse or blood pressure was observed. Ipratropium appears to be an important addition to the bronchodilator agents used in isoproterenol-responsive obstructive pulmonary disease.

The effect of disodium cromoglycate and Sch 1000 on exercise-induced asthma was studied in nine patients. The exercise stimulus consisted of either treadmill running or jogging; spirometric measurements were made before and at intervals after exercise. In six patients, disodium cromoglycate and Sch 1000 were both effective in preventing exercise-induced asthma. In two patients, Sch 1000 was effective, while disodium cromoglycate gave no protection. In the remaining patient, disodium cromoglycate was more effective than Sch 1000. The findings of this study suggest that the mechanism of exercise-induced asthma may be multifactorial, and the relative importance of each factor may vary in different patients.

Terbutaline, a new bronchodilator drug reported to have selective affinity for beta 2-adrenergic receptors, was compared with epinephrine in the treatment of 49 adult subjects with acute bronchial asthma. Under double-blind conditions, 24 subjects received 1.0 mg of terbutaline sulfate, and 25 subjects received 0.5 mg of epinephrine hydrochloride subcutaneously. Spirometric measurements, heart rate, and blood pressure, as well as subjective responses, were recorded prior to, and then at 5, 15, 30, 60, and 120 minutes after administration of the drug. The results indicate that terbutaline is an effective bronchodilator drug in subjects with acute asthma; however, the heart rate rose significantly after administration of terbutaline, with a maximal increase of 25 percent above control. Review of the literature reveals that tachycardia is a consistent finding when subcutaneous doses of terbutaline in excess of 0.25 mg are administered. Stimulation of beta 1-adrenergic receptors in the heart appears to be the most important factor involved in this response. A lesser cardioaccelerator effect was observed after administering epinephrine in a dose producing an equivalent degree of bronchodilatation.

A 5-percent solution of the sympathomimetic bronchodilator, metaproterenol sulfate (Alupent) was evaluated by comparison with an 0.5-percent solution of isoproterenol in a double-blind crossover study before and after 60 days of inhalation of metaproterenol administered at least four times daily via a hand-bulb nebulizer. Data from tests of pulmonary function obtained in 27 asthmatic patients indicated that metaproterenol sulfate in this dose form surpassed isoproterenol in the duration of effect after seven weeks of continuous administration. Side effects did not necessitate the interruption of metaproterenol therapy. No evidence of the development of tolerance to the drug was shown by any of the patients at the end of the study.

The clinical results and changes in sputum found in both a short-term inpatient trial and a subsequent long-term outpatient investigation (three-month double-blind controlled study) of 82 patients with chronic bronchitis treated with a new mucolytic agent, S-carboxymethylcysteine (Mucodyne), are reported. Fluidification of sputum with reduction in certain measurements of the viscosity of morning sputum aliquots, associated with improvement in the ability to cough up bronchial secretions, significant increase in sputum volume output, and improvement in ventilation (as estimated by the forced expiratory volume in one second), were observed in both trials as dose-related responses, with an increase in the ease of expectoration and a reduction in cough frequency and dyspnea. Therapy with S-carboxymethylcysteine was well tolerated, and there were no serious adverse effects, either immediate or delayed. We suggest that the effect of the drug in fluidifying sputum may be due to a mucoregulatory mechanism which reverses the sputum macromolecular disturbances seen in chronic bronchitis.

A simplified method for estimation of one-minute oxygen uptake (VO2-1) during treadmill grade walking at vertical power requirements of 250, 750, and 1,000 kg-meters/min was devised, where power=weight (kg) X grade (fractional) X walking speed. All subjects were men. There were 29 controls, 34 subjects with coronary arterial disease (of whom 18 had had myocardial infarction), nine subjects with diffuse pulmonary disease, and four subjects with ischemic vascular disease. Abnormally reduced values for VO2-1 were related to these diseases and, more specifically, to a history of myocardial infarction and (in pulmonary subjects) to reduced single-breath diffusing capacity. Lowest values of VO2-1 for a group were found in ischemic vascular disease. Reduced response of VO2-1 may therefore be caused by central defects of oxygen transport.

We performed a double-blind study on the effect of oral administration of 10 mg of delta9-tetrahydrocannabinol on specific airway conductance (Gaw/VL) and the maximal expiratory flow at 50% of vital capacity (Vmax 50%) in six control and six asthmatic subjects. In control subjects, there was a slight but statistically significant increase in Gaw/VL after oral administration of delta9-tetrahydrocannabinol; however, there was no significant increase in Vmax 50%. One of the asthmatic patients developed severe bronchoconstriction following administration of delta9-tetrahydrocannabinol; among the remaining five patients, there were variable changes in Gaw/VL and Vmax 50% after oral administration of delta9-tetrahydrocannabinol, but mean changes were not significant. Mild effects on the central nervous system (CNS) were observed in three subjects; six subjects, three of whom had unpleasant mood changes, had more prominent CNS effects. We concluded that oral administration of delta9-tetrahydrocannabinol is unlikely to be of therepeutic value in asthma, since its bronchodilator action was mild and inconstant and was associated with significant CNS effects. Moreover, one asthmatic patient developed severe bronchoconstriction following oral administration of delta 9-tetrahydrocannabinol.

In a single-blind study the short-term effects of oral administration of Th1165a (5, 10, 15, and 20 mg), metaproterenol sulfate (Alupent) (20 mg), and placebo on ventilatory function, pulse rate, and systolic and diastolic blood pressure were compared over a period of six hours in ten patients with stable, reversible obstructive airway disease. Both Th1165a (5, 10, 15 and 20 mg) and metaproterenol administration caused significant bronchodilation of rapid onset (30 minutes), but the bronchodilator effect of Th1165a (10, 15, and 20 mg) was greater and lasted longer (six hours vs three hours) than that of metaproterenol. A dose-dependent bronchodilator effect was recognizable after administration of Th1165a. The 20-mg dose of metaproterenol sulfate and the 5-mg and 10-mg doses of Th1165a produced minimal side effects. Larger doses (15 and 20 mg of Th1165a caused significant increases in pulse rate. Mild and transient tremors were the most common side effect after administration of Th1165a.

In a randomized double-blind 12-week trial of steroid-dependent patients with chronic asthma, ten (59 percent) out of 17 patients receiving beclomethasone dipropionate aerosol in a total daily dose of 400mug were able to discontinue systemic corticosteroid therapy successfully, compared to two (13 percent) out of 15 patients in the placebo group (P=0.002). At the end of the trial, the average 8 am plasma cortisol level in the group receiving beclomethasone was more than twice the pretherapy value, whereas the level in the placebo group showed no significant change. There was no significant difference between the beclomethasone group and the placebo group in the overall incidence of side effects related to the aerosol and the effects of systemic corticosteroid withdrawal. Oral candidiasis was not found in any patient receiving beclomethasone dipropionate aerosol. Allergic nasal symptoms were disabling in many patients when the oral dosage of corticosteroids was tapered.

In order to objectively document the accepted clinical efficacy of ampicillin in treating bacterial exacerbations of chronic bronchitis, as well as to evaluate the efficacy of methacycline, a double-blind crossover study was designed. Twenty patients with chronic bronchial disease were treated for two separate acute bacterial exacerbations, once with 2 gm of ampicillin daily, and once with 600 mg of methacycline daily, for 14 days. There were a few significant differences when comparing the efficacy of the antimicrobials. For example, the daily volume of sputum significantly went from 35.6 ml initially to 20.5 ml at the end of treatment with methacycline, and from 37.4 to 18.0 ml with ampicillin. Sputum neutrophils excreted per day went from 446 to 147 million with methacycline and from 433 to 94 million with ampicillin. Gram-positive diplococci and cocci on gram stains of sputum significantly decreased form 10.6 to 3.3 with methacycline and from 16.8 to 2.1 with ampicillin. This investigation objectively documents with accepted clinical efficacy of ampicillin and proves methacycline to be an equally effective agent.

Twenty-five steroid-dependent severely asthmatic patients, ranging in age from 20 to 67 years, were hospitalized. Baseline laboratory and pulmonary function testing was followed by reduction of prednisone therapy to 5 mg daily and by entry into a randomized double-blind study of placebo vs active aerosol triamcinolone acetonide (300mug four times daily). In this four-week trial, aerosol triamcinolone acetonide further reversed airway obstruction and proved to be an effective substitute for large oral doses of steroids in steroid-dependent patients with severe asthma. No significant improvement occurred in the maximum midexpiratory flow or the maximum velocity of air flow after 50 percent or 75 percent of the vital capacity had been expelled. There was no significant difference in the frequency of untoward effects between the groups taking aerosol triamcinolone acetonide and its vehicle. No patient demonstrated any definite return of adrenal function.

Twenty-seven patients underwent studies of unilateral lung function by the lateral-position test (LPT) and by computer-analyzed radionuclide imaging of ventilation and perfusion. The patients were divided into two groups, symmetric or asymmetric, on the basis of the physical examination of the chest and the chest radiograph. In patients with symmetry, the estimate of unilateral lung function by the LPT and isotopic estimates for unilateral lung volume, unilateral distribution of tidal volume, and unilateral perfusion, agreed within 2 percent, 4 percent, and 3 percent, respectively. In patients with asymmetry, the differences were 9 percent, 8 percent, and 13 percent. In settings of marked unilateral ventilation-perfusion imbalance, the LPT primarily reflected ventilation. Prediction of unilateral ventilatory function based upon the LPT and spirometric measurements agreed closely with unilateral ventilation determined isotopically by 133xenon, even in the presence of chronic obstructive lung disease. Our results confirm that the LPT provides valid information about unilateral lung function.

Sixteen men with well-documented angina pectoris and without previous myocardial infarction performed a multistage exercise stress test to determine their levels of exercise-induced limitations, characterized by onset of chest discomfort or electrocardiographic ischemic changes, or both. Following a control study, each subject was assigned randomly to either a placebo- or vasodilator-treated group, received chewable medication, and was retested 30 minutes after chewing the medication. Blood pressure, heart rate, and electrocardiographic changes were measured during rest, peak exercise, and recovery. A phonocardiogram, carotid-pulse contour, and single-lead electrocardiogram were recorded simultaneously at supine rest before and immediately after exercise, and systolic time intervals were measured. Results indicated that chewable isosorbide dinitrate reduced systolic blood pressure and the triple product (systolic blood pressure X heart rate X ejection time) significantly during rest and reduced the left ventricular ejection time corrected for heart rate both at rest and peak exercise; no significant differences were observed in the placebo group. The ability to achieve an increased workload was observed in both groups, and the threshold for ischemic manifestations occurred at comparable triple-product levels in both during pretreatment and posttreatment studies.

The hemodynamic response to nitroglycerin administration, to sublingual or oral administration of isosorbide dinitrate, or to a placebo was evaluated and compared in 37 patients with unstable angina pectoris under resting, pain-free conditions. Patients with congestive heart failure were not included in this study. Serial measurements of mean arterial blood pressure (MAP), pulmonary arterial end-diastolic pressure (PAEDP), cardiac index (CI), and heart rate (HR) were obtained for one hour following nitroglycerin administration and for four hours following sublingual or oral administration of isosorbide dinitrate. Echocardiographic end-diastolic volume (EDV) measurements were obtained for the groups receiving isosorbide dinitrate or placebo. There was a significant (P less than 0.05 or less than 0.1) reduction of the MAP (5 to 10 mm Hg) that persisted for more than four hours following both sublingual and oral administration of isosorbide dinitrate. The changes in the PAEDP, HR, and CI following sublingual or oral administration of isosorbide dinitrate were small and not significant. In the group receiving isosorbide dinitrate sublingually, the EDV was reduced by more than 30 ml below the placebo group (P less than 0.1) for up to four hours. The effects of nitroglycerin administration were similar in magnitude but of much shorter duration (three to four hours for sublingual and oral administration of isosorbide dinitrate vs 15 to 30 minutes for nitroglycerin). These data demonstrate that the duration of the hemodynamic effects of sublingually and orally administered isosorbide dinitrate in patients with unstable angina pectoris and normal resting hemodynamics is 8 to 12 times longer than that of nitroglycerin.

A double-blind study of the effects of phlebotomy was carried out in 18 patients with polycythemia secondary to severe hypoxemic lung disease. Eleven subjects underwent a single phlebotomy of 10 percent of their blood volume, and eight patients serving as controls underwent a sham procedure. Eight of the phlebotomized subjects, but none of the controls, reported subjective clinical improvement (P less than 0.005). Subjects who noted improvement after venesection had higher hematocrit readings than those who did not (P less than 0.02). Symptomatic relief seemed to be most dramatic in those with clinical evidence of congestive heart failure. In contrast to this clear-cut subjective improvement, phlebotomy did not alter objective indices of airway obstruction, lung elastic recoil, pulmonary gas exchange, or exercise tolerance in either the phlebotomized or the control group. Thus, although phlebotomy produced subjective benefit in the majority of patients studied, it was not associated with objective improvement in lung function or exercise tolerance.

Endotracheal administration of gentamicin has been compared to the endotracheal administration of aminosidin plus polymyxin B as a preventive measure against tracheobronchial infections in 25 and 22 tracheotomized patients respectively who had been admitted to a neurosurgical unit. Both series were comparable as far as underlying disease, duration of hospitalization, surgical therapy. Both regimens were similarly effective from the bacteriologic and clinical points of view. Both regimens were similarly effective in preventing colonization of bronchial secretions by potential pathogens and were associated with a similar frequency of infectious episodes (eight in each group). The use of aminosidin-polymyxin B combination was associated with a lower incidence of emergence of gentamicin resistant strains, but the endotracheal administration of gentamicin was better tolerated than that of the combination. It is concluded that the combination of aminosidin-polymyxin is a useful alternative to gentamicin for the prevention of bronchopulmonary infections in unconscious tracheotomized patients.